P703: ASSOCIATION BETWEEN BARIATRIC SURGERY AND OUTCOMES IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA TREATED WITH ORAL TYROSINE KINASE INHIBITORS
Authors: F. Haddad, H. Kantarjian, E. Jabbour, N. Short, A. Bidikian, J. Ning, L. Xiao, N. Pemmaraju, K. Marx, F. Ravandi, K. Sasaki, G. Issa
Journal: HemaSphere (2022)

Background: Bariatric surgery is widely used in patients (pts) with morbid obesity with great success in reduction of associated metabolic complications. However, it can also alter the pharmacokinetics of oral medications. Oral tyrosine kinase inhibitors (TKIs) represent the mainstay of chronic myeloid leukemia (CML) therapy. The impact of bariatric surgery on CML treatment outcomes is largely unknown. Aims: To evaluate the clinical impact of bariatric surgery on outcomes of CML pts treated with TKIs. Methods: In a retrospective analysis, we screened pts with CML treated at our institution and identified those who had any type of bariatric surgery including gastric bypass, gastric sleeve or gastric banding. We then compared their responses and outcomes to a control cohort of pts without history of bariatric surgery, using propensity score matching for Sokal Risk and body mass index (BMI) at a 2:1 ratio. In addition to cytogenetic and molecular responses, we assessed times to achieving responses and BCR::ABL1 halving times to investigate differences in response dynamics. We assessed comorbidities using the Charlson Comorbidity Index. Event-free survival (EFS) was measured from treatment start to loss of response, progression, or death, whereas failure-free survival (FFS) additionally accounted for therapy discontinuation for other reasons such as intolerance. Overall survival (OS) was measured from treatment start date to death or censored at last follow-up. Univariate and multivariate analyses (MVA) were used to assess the association between characteristics and survival outcomes. Results: We identified 28 pts with CML and a history of bariatric surgery (22 pts had their surgery before the diagnosis of CML) and 56 pts as a matched control. Their baseline characteristics are summarized below. Among pts with bariatric surgery, 61% required >1 TKI throughout the course of their disease due to intolerance or resistance, compared with 25% of the control group (P=0.002). BCR::ABL1 halving time was higher in the bariatric surgery group vs control (26 days vs 13 days; P<0.0001), suggesting slower response dynamics. The median time to achieve complete cytogenetic response (CCyR) and major molecular response (MMR) was significantly longer in pts with history of bariatric surgery: 6 months vs 3 months (P<0.0001) and 12 months vs 6 months (P=0.001), respectively. Bariatric surgery was associated with inferior EFS (10-year: 31% vs 69%; P=0.009) and FFS (10-year: 16% vs 54%; P<0.0001) compared with control, with a trend for worse OS (10-year: 65% vs 85%; P=0.09) (Figure 1). We subsequently conducted univariate and MVA and assessed the impact of bariatric surgery and covariates such as sex, BMI, Sokal risk, TKI used, age and use of proton pump inhibitors. Bariatric surgery was the only independent predictor for the risk of treatment failure (hazard ratio [HR] 5.95, 95% CI 2.38-14.89; P=0.0001) or EFS (HR 3.6, 95% CI 1.38-7.91; P=0.007) in the MVA but did not independently affect the risk of death. The Charlson Comorbidity Index was the only independent predictor for the risk of death (HR 1.65, 95% CI 1.10-2.48; P=0.02). Image:Summary/Conclusion: Bariatric surgery is associated with slower responses to TKIs and higher rates of treatment failure. There is an unmet need to design treatment strategies for these patients. Although not readily available in the clinical setting, studies measuring drug level in these patients are needed to assess which TKI has a better bioavailability, which in turn could translate to improved outcomes.